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dc.contributor.advisorO'Hagan, David
dc.contributor.authorChan, K. K. Jason
dc.coverage.spatialxi, 253en_US
dc.date.accessioned2014-02-27T15:11:51Z
dc.date.available2014-02-27T15:11:51Z
dc.date.issued2013
dc.identifieruk.bl.ethos.595614 
dc.identifier.urihttps://hdl.handle.net/10023/4478
dc.description.abstractThis thesis is focussed on the biosynthesis of three toxins: fluoroacetate, 4-fluoro-L-theronine and β-ethynyl-L-serine which are biosynthesised by the soil bacteria Streptomyces cattleya. The two fluorinated metabolites originate from a common biosynthetic pathway and the thesis describes studies carried out on an aldose-ketose isomerase enzyme of the pathway. The biosynthetic origin of β-ethynyl-L-serine is not known. A total synthesis of this acetylenic amino acid is descibed along with the development of a new analytical method for identifying the metabolite and for future isotope-labelling based biosynthetic studies. Chapter 1 presents the background of this research. It is focussed on the biosynthesis of fluoroacetate and 4-fluoro-L-threonine by S. cattleya and it also introduces alkyne-containing natural products and their biosynthesis. Chapter 2 describes the work carried out on crystallisation of the aldose-ketose isomerase of the fluorometabolite pathway in S. cattleya. Crystals of the isomerase were obtained and they were diffracted by X-ray, however a structure could not be solved. Chapter 3 contains site-directed mutagenesis studies of the isomerase from S. cattleya. Chapter 4 describes an enantioselective total synthesis of β-ethynyl-L-serine. A robust analytical technique based on derivatisation using 'Click' chemistry and LC-MS was developed for the detection of this amino acid directly from the fermentation broth. Chapter 5 details the experimental procedures for compounds synthesised in this thesis and the biological procedures for gene cloning and protein purification.en_US
dc.language.isoenen_US
dc.publisherUniversity of St Andrews
dc.subjectStreptomyces cattleyaen_US
dc.subjectFluorometaboliteen_US
dc.subjectOrganofluorine natural productsen_US
dc.subjectIsomeraseen_US
dc.subjectFluorinaseen_US
dc.subjectProtein crystallographyen_US
dc.subjectEthynylserineen_US
dc.subjectRare amino acidsen_US
dc.subjectClick chemistryen_US
dc.subjectAcetylenic amino aciden_US
dc.subject.lccQR88.3C5
dc.subject.lcshStreptomyces--Metabolismen_US
dc.subject.lcshMicrobiological synthesisen_US
dc.subject.lcshToxins--Synthesisen_US
dc.subject.lcshAmino acids--Synthesisen_US
dc.subject.lcshIsomerasesen_US
dc.titleIdentification and enzyme studies of rare amino acid biosynthesis from Streptomyces cattleyaen_US
dc.typeThesisen_US
dc.type.qualificationlevelDoctoralen_US
dc.type.qualificationnamePhD Doctor of Philosophyen_US
dc.publisher.institutionThe University of St Andrewsen_US


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